Journal
SCIENCE IMMUNOLOGY
Volume 7, Issue 73, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abq3511
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Funding
- NCI Cancer Center Support Grant [5P30 CA023108-41]
- Swedish Research Council [2020-06235, 2021-04665]
- SciLifeLab National COVID-19 Research Program - Knut and Alice Wallenberg Foundation [VC-2020-0015]
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This study analyzed the antibody response after Omicron/BA.1 infection in mRNA-vaccinated donors. The findings highlighted strong immune responses and recognition of SARS-CoV-2 variant strains, emphasizing the early role of vaccine-induced memory B cells.
Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses after Omicron/BA.1 infection in messenger RNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.
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